Pharmacokinetic modeling of solid and hollow gold-coated superparamagnetic iron oxide nanoparticles for brain-targeted therapeutics: prediction and experiment

IF 23.2 2区材料科学 Q1 MATERIALS SCIENCE, COMPOSITES

Advanced Composites and Hybrid Materials Pub Date : 2024-04-22 DOI:10.1007/s42114-024-00884-9

Hanwen Hu, Muzhaozi Yuan, Jingfan Chen, Tianzhu Fan, Nguyen Nguyen, Caitlin A. Madison, Tianhao Yan, Zhifeng Xiao, Ying Li, Shoshana Eitan, Hong-cai Zhou, Jean Phillippe Pellois, Ya Wang

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引用次数: 0

Abstract

Magneto-plasmonic nanoparticles (MPNPs), such as solid gold (Au) or hollow gold (HG) coated superparamagnetic iron oxide (SPIO) nanoparticles (NPs), have attracted increasing attention for brain-targeted therapeutics. This is due to their supreme magnetic targeting capability, light-to-heat conversion efficiency, and biocompatibility. Though promising, their therapeutic efficiency is difficult to predict because of the complex absorption, distribution, metabolism, and excretion process and the intrinsic and extrinsic properties of the blood–brain barrier (BBB). This paper presents a modern physiologically based pharmacokinetic (PBPK) model to predict pharmacokinetic (PK) behaviors of brain-targeting MPNPs and investigate their morphology and surface function-dependent BBB crossing efficiency. This model quantifies intrinsic and extrinsic properties of PK parameters, including phagocytic cellular uptake rate and brain permeability. This model successfully predicts the biodistribution of functionalized Au-SPIO (18.42 ± 0.23 nm) and HG-SPIO (73.65 ± 1.46 nm) MPNPs in 8-week-old adult mice in a 16-h window after intraperitoneal (IP) injection. These predictions agree well with the experimental data with a low absolute average fold error (1.5381 for Au-SPIO and 1.1225 for HG-SPIO NPs). Interestingly, Au-SPIO MPNPs with thinner plasmonic layers result in higher magnetization levels and thus lead to more efficient BBB crossing. Static magnetic field stimulation could improve brain accumulation of IP-injected Au-SPIO and HG-SPIO NPs by up to 4.9% and 1.4%, respectively. Additionally, IP injection led to higher brain accumulation compared to intravenous injection. This modern PBPK model can guide MPNP design optimization for brain-specific therapeutics.

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用于脑靶向治疗的固态和空心金涂层超顺磁性氧化铁纳米粒子的药代动力学模型：预测与实验

磁塑纳米粒子（MPNPs），如实心金（Au）或空心金（HG）包覆的超顺磁性氧化铁（SPIO）纳米粒子（NPs），在脑靶向治疗方面吸引了越来越多的关注。这是因为它们具有超强的磁性靶向能力、光-热转换效率和生物相容性。尽管前景广阔，但由于其复杂的吸收、分布、代谢和排泄过程以及血脑屏障（BBB）的内在和外在特性，其治疗效率难以预测。本文介绍了一种基于生理学的现代药代动力学（PBPK）模型，用于预测脑靶向 MPNPs 的药代动力学（PK）行为，并研究其形态和表面功能依赖的 BBB 穿越效率。该模型量化了 PK 参数的内在和外在特性，包括吞噬细胞摄取率和脑通透性。该模型成功预测了功能化 Au-SPIO（18.42 ± 0.23 nm）和 HG-SPIO（73.65 ± 1.46 nm）MPNPs 在 8 周大的成年小鼠腹腔注射 16 小时后的生物分布。这些预测与实验数据非常吻合，绝对平均折叠误差较低（Au-SPIO 为 1.5381，HG-SPIO NPs 为 1.1225）。有趣的是，Au-SPIO MPNPs 的电浆层较薄，磁化水平较高，因此能更有效地穿过 BBB。静态磁场刺激可使 IP 注入的 Au-SPIO 和 HG-SPIO NPs 的脑积聚率分别提高 4.9% 和 1.4%。此外，与静脉注射相比，IP注射的脑累积率更高。这一现代 PBPK 模型可指导脑特异性疗法的 MPNP 设计优化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advanced Composites and Hybrid Materials Multiple-

CiteScore

26.00

自引率

21.40%

发文量

185

期刊介绍： Advanced Composites and Hybrid Materials is a leading international journal that promotes interdisciplinary collaboration among materials scientists, engineers, chemists, biologists, and physicists working on composites, including nanocomposites. Our aim is to facilitate rapid scientific communication in this field. The journal publishes high-quality research on various aspects of composite materials, including materials design, surface and interface science/engineering, manufacturing, structure control, property design, device fabrication, and other applications. We also welcome simulation and modeling studies that are relevant to composites. Additionally, papers focusing on the relationship between fillers and the matrix are of particular interest. Our scope includes polymer, metal, and ceramic matrices, with a special emphasis on reviews and meta-analyses related to materials selection. We cover a wide range of topics, including transport properties, strategies for controlling interfaces and composition distribution, bottom-up assembly of nanocomposites, highly porous and high-density composites, electronic structure design, materials synergisms, and thermoelectric materials. Advanced Composites and Hybrid Materials follows a rigorous single-blind peer-review process to ensure the quality and integrity of the published work.